TW202136516A - Iva型黏多醣病之治療 - Google Patents
Iva型黏多醣病之治療 Download PDFInfo
- Publication number
- TW202136516A TW202136516A TW110103306A TW110103306A TW202136516A TW 202136516 A TW202136516 A TW 202136516A TW 110103306 A TW110103306 A TW 110103306A TW 110103306 A TW110103306 A TW 110103306A TW 202136516 A TW202136516 A TW 202136516A
- Authority
- TW
- Taiwan
- Prior art keywords
- nucleotide sequence
- seq
- promoter
- hgalns
- raav
- Prior art date
Links
- 208000012253 mucopolysaccharidosis IVA Diseases 0.000 title claims abstract description 128
- 238000011282 treatment Methods 0.000 title abstract description 50
- 208000025797 Mucopolysaccharidosis type 4A Diseases 0.000 title abstract description 5
- 101001066305 Homo sapiens N-acetylgalactosamine-6-sulfatase Proteins 0.000 claims abstract description 539
- 241000702421 Dependoparvovirus Species 0.000 claims abstract description 199
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 claims abstract description 129
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 129
- 238000000034 method Methods 0.000 claims abstract description 111
- 239000002773 nucleotide Substances 0.000 claims description 1197
- 125000003729 nucleotide group Chemical group 0.000 claims description 1197
- 102000049489 human GALNS Human genes 0.000 claims description 520
- 108090000623 proteins and genes Proteins 0.000 claims description 395
- 230000009261 transgenic effect Effects 0.000 claims description 244
- 210000004185 liver Anatomy 0.000 claims description 199
- 102000040430 polynucleotide Human genes 0.000 claims description 197
- 108091033319 polynucleotide Proteins 0.000 claims description 197
- 239000002157 polynucleotide Substances 0.000 claims description 197
- 230000014509 gene expression Effects 0.000 claims description 190
- 108010038807 Oligopeptides Proteins 0.000 claims description 105
- 102000015636 Oligopeptides Human genes 0.000 claims description 105
- 108020001507 fusion proteins Proteins 0.000 claims description 98
- 102000037865 fusion proteins Human genes 0.000 claims description 97
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 87
- 210000004027 cell Anatomy 0.000 claims description 86
- 230000002378 acidificating effect Effects 0.000 claims description 72
- 239000003623 enhancer Substances 0.000 claims description 69
- 102000006734 Beta-Globulins Human genes 0.000 claims description 61
- 108010087504 Beta-Globulins Proteins 0.000 claims description 61
- 210000002706 plastid Anatomy 0.000 claims description 60
- 230000008488 polyadenylation Effects 0.000 claims description 53
- 102000013918 Apolipoproteins E Human genes 0.000 claims description 51
- 108010025628 Apolipoproteins E Proteins 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 47
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 39
- 102000006395 Globulins Human genes 0.000 claims description 30
- 108010044091 Globulins Proteins 0.000 claims description 30
- 210000003494 hepatocyte Anatomy 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 18
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 17
- 108091029430 CpG site Proteins 0.000 claims description 13
- 239000002777 nucleoside Substances 0.000 claims description 13
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 13
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 9
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 9
- 102100021519 Hemoglobin subunit beta Human genes 0.000 claims description 8
- 108091005904 Hemoglobin subunit beta Proteins 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000001415 gene therapy Methods 0.000 abstract description 39
- 102100031688 N-acetylgalactosamine-6-sulfatase Human genes 0.000 abstract description 18
- 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 abstract description 3
- 101150010487 are gene Proteins 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 228
- 230000000694 effects Effects 0.000 description 97
- 210000000234 capsid Anatomy 0.000 description 92
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 66
- 210000001519 tissue Anatomy 0.000 description 54
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 52
- 102000002248 Thyroxine-Binding Globulin Human genes 0.000 description 51
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 51
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 50
- 229920000288 Keratan sulfate Polymers 0.000 description 49
- 210000000845 cartilage Anatomy 0.000 description 47
- 210000003709 heart valve Anatomy 0.000 description 45
- 210000004349 growth plate Anatomy 0.000 description 43
- 102000004190 Enzymes Human genes 0.000 description 34
- 108090000790 Enzymes Proteins 0.000 description 34
- 229940088598 enzyme Drugs 0.000 description 34
- 125000003275 alpha amino acid group Chemical group 0.000 description 33
- 210000004072 lung Anatomy 0.000 description 33
- 230000005499 meniscus Effects 0.000 description 33
- 210000003041 ligament Anatomy 0.000 description 31
- 210000000952 spleen Anatomy 0.000 description 29
- 210000003734 kidney Anatomy 0.000 description 28
- 210000004165 myocardium Anatomy 0.000 description 27
- 210000001612 chondrocyte Anatomy 0.000 description 22
- 210000003437 trachea Anatomy 0.000 description 22
- 239000013598 vector Substances 0.000 description 22
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 19
- 229920002683 Glycosaminoglycan Polymers 0.000 description 19
- 201000010099 disease Diseases 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 230000003612 virological effect Effects 0.000 description 17
- 239000013607 AAV vector Substances 0.000 description 16
- 238000001890 transfection Methods 0.000 description 16
- 238000002641 enzyme replacement therapy Methods 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 14
- 230000007170 pathology Effects 0.000 description 13
- 108700019146 Transgenes Proteins 0.000 description 12
- 238000010172 mouse model Methods 0.000 description 12
- 210000003205 muscle Anatomy 0.000 description 12
- 238000003860 storage Methods 0.000 description 12
- 239000000090 biomarker Substances 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 102000053602 DNA Human genes 0.000 description 9
- 108091092195 Intron Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 210000001188 articular cartilage Anatomy 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 238000002650 immunosuppressive therapy Methods 0.000 description 9
- 229920001287 Chondroitin sulfate Polymers 0.000 description 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 210000005229 liver cell Anatomy 0.000 description 8
- 230000008685 targeting Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 241000649046 Adeno-associated virus 11 Species 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 230000003902 lesion Effects 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 210000002303 tibia Anatomy 0.000 description 7
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 6
- 101150050387 Galns gene Proteins 0.000 description 6
- 108091023045 Untranslated Region Proteins 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 235000003704 aspartic acid Nutrition 0.000 description 6
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 6
- 230000001506 immunosuppresive effect Effects 0.000 description 6
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 5
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 5
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 5
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 5
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 108020004682 Single-Stranded DNA Proteins 0.000 description 5
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 210000000629 knee joint Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 5
- 229960000951 mycophenolic acid Drugs 0.000 description 5
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 5
- 229960001967 tacrolimus Drugs 0.000 description 5
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 5
- 210000000689 upper leg Anatomy 0.000 description 5
- 230000002477 vacuolizing effect Effects 0.000 description 5
- 108090000565 Capsid Proteins Proteins 0.000 description 4
- 102100023321 Ceruloplasmin Human genes 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- 241001227561 Valgus Species 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 4
- 101100348617 Candida albicans (strain SC5314 / ATCC MYA-2876) NIK1 gene Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 101000640899 Homo sapiens Solute carrier family 12 member 2 Proteins 0.000 description 3
- 208000005137 Joint instability Diseases 0.000 description 3
- 206010070874 Joint laxity Diseases 0.000 description 3
- 206010023509 Kyphosis Diseases 0.000 description 3
- 238000011887 Necropsy Methods 0.000 description 3
- 101100007329 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS1 gene Proteins 0.000 description 3
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 3
- 206010072610 Skeletal dysplasia Diseases 0.000 description 3
- 210000001306 articular ligament Anatomy 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 208000016354 hearing loss disease Diseases 0.000 description 3
- 238000007489 histopathology method Methods 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 210000003098 myoblast Anatomy 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 239000013647 rAAV8 vector Substances 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 241000649045 Adeno-associated virus 10 Species 0.000 description 2
- 206010061728 Bone lesion Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 208000032170 Congenital Abnormalities Diseases 0.000 description 2
- 208000006069 Corneal Opacity Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 229920002971 Heparan sulfate Polymers 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- 206010061307 Neck deformity Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 206010041549 Spinal cord compression Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 231100000269 corneal opacity Toxicity 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004821 effect on bone Effects 0.000 description 2
- 238000009585 enzyme analysis Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 208000018578 heart valve disease Diseases 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000006058 immune tolerance Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 210000001865 kupffer cell Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000002132 lysosomal effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000004115 mitral valve Anatomy 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000002250 progressing effect Effects 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000003934 vacuole Anatomy 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 101150044789 Cap gene Proteins 0.000 description 1
- 208000034869 Cervical myelopathy Diseases 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
- 108010031792 IGF Type 2 Receptor Proteins 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000029836 Inguinal Hernia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- 206010023204 Joint dislocation Diseases 0.000 description 1
- 101150094051 KO gene Proteins 0.000 description 1
- 208000007623 Lordosis Diseases 0.000 description 1
- 102000019218 Mannose-6-phosphate receptors Human genes 0.000 description 1
- 241001272720 Medialuna californiensis Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101100282100 Mus musculus Galns gene Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 101710099863 N-acetylgalactosamine-6-sulfatase Proteins 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 101710196809 Non-specific lipid-transfer protein 1 Proteins 0.000 description 1
- 101710196810 Non-specific lipid-transfer protein 2 Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000020221 Short stature Diseases 0.000 description 1
- 108010043267 Sp7 Transcription Factor Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 206010044291 Tracheal obstruction Diseases 0.000 description 1
- 102100032317 Transcription factor Sp7 Human genes 0.000 description 1
- 108091034131 VA RNA Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 210000003683 corneal stroma Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000001513 elbow Anatomy 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 210000003035 hyaline cartilage Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000007235 immunity generation Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000000236 metacarpal bone Anatomy 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000001423 neocortical effect Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940000673 orphan drug Drugs 0.000 description 1
- 239000002859 orphan drug Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 101150066583 rep gene Proteins 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003307 reticuloendothelial effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 206010039722 scoliosis Diseases 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 231100001055 skeletal defect Toxicity 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 239000011232 storage material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 210000004926 tubular epithelial cell Anatomy 0.000 description 1
- 210000000623 ulna Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/06—Sulfuric ester hydrolases (3.1.6)
- C12Y301/06004—N-Acetylgalactosamine-6-sulfatase (3.1.6.4)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/22—Vectors comprising a coding region that has been codon optimised for expression in a respective host
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/15—Vector systems having a special element relevant for transcription chimeric enhancer/promoter combination
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202062967499P | 2020-01-29 | 2020-01-29 | |
| US62/967,499 | 2020-01-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202136516A true TW202136516A (zh) | 2021-10-01 |
Family
ID=74673384
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110103306A TW202136516A (zh) | 2020-01-29 | 2021-01-28 | Iva型黏多醣病之治療 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20230064077A1 (enExample) |
| EP (1) | EP4097238A1 (enExample) |
| JP (1) | JP2023512043A (enExample) |
| KR (1) | KR20220133900A (enExample) |
| AR (1) | AR121201A1 (enExample) |
| AU (1) | AU2021212749A1 (enExample) |
| BR (1) | BR112022015036A2 (enExample) |
| CA (1) | CA3168251A1 (enExample) |
| IL (1) | IL294638A (enExample) |
| TW (1) | TW202136516A (enExample) |
| WO (1) | WO2021154956A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202039857A (zh) | 2018-07-27 | 2020-11-01 | 美商銳進科斯生物股份有限公司 | 黏多醣病iva之治療 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2369002A1 (en) | 1999-08-09 | 2011-09-28 | Targeted Genetics Corporation | Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms intrastrand base pairs |
| SG10202108118RA (en) | 2001-11-13 | 2021-08-30 | Univ Pennsylvania | A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby |
| ES2975413T3 (es) | 2001-12-17 | 2024-07-05 | Univ Pennsylvania | Secuencias de serotipo 8 de virus adenoasociado (AAV), vectores que las contienen y usos de las mismas |
| HUE054805T2 (hu) | 2003-09-30 | 2021-09-28 | Univ Pennsylvania | Adeno-asszociált vírus (AAV) kládok, szekvenciák, az azokat tartalmazó vektorok és alkalmazásaik |
| EP3085389A1 (en) | 2005-04-07 | 2016-10-26 | The Trustees Of The University Of Pennsylvania | Method of increasing the function of an aav vector |
| WO2006132118A1 (ja) | 2005-06-09 | 2006-12-14 | Matsushita Electric Industrial Co., Ltd. | 振幅誤差補償装置及び直交度誤差補償装置 |
| WO2010138263A2 (en) | 2009-05-28 | 2010-12-02 | University Of Massachusetts | Novel aav 's and uses thereof |
| US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| US8628966B2 (en) | 2010-04-30 | 2014-01-14 | City Of Hope | CD34-derived recombinant adeno-associated vectors for stem cell transduction and systemic therapeutic gene transfer |
| CN107828820B (zh) | 2010-10-27 | 2022-06-07 | 学校法人自治医科大学 | 用于向神经系统细胞导入基因的腺相关病毒粒子 |
| US9409953B2 (en) | 2011-02-10 | 2016-08-09 | The University Of North Carolina At Chapel Hill | Viral vectors with modified transduction profiles and methods of making and using the same |
| CN107012171B (zh) | 2011-04-22 | 2021-07-13 | 加利福尼亚大学董事会 | 具有变异衣壳的腺相关病毒病毒体及其使用方法 |
| EP3147295B2 (en) | 2011-08-24 | 2023-11-22 | The Board of Trustees of the Leland Stanford Junior University | New avv capsid proteins for nucleic acid transfer |
| EP3470523A1 (en) | 2012-05-09 | 2019-04-17 | Oregon Health & Science University | Adeno associated virus plasmids and vectors |
| CA2905952A1 (en) | 2013-03-13 | 2014-10-02 | The Children's Hospital Of Philadelphia | Adeno-associated virus vectors and methods of use thereof |
| PT3024498T (pt) | 2013-07-22 | 2020-03-06 | Childrens Hospital Philadelphia | Variante aav e composições, métodos e usos para transferência genética em células, órgãos e tecidos |
| EP3564379A1 (en) | 2013-09-13 | 2019-11-06 | California Institute of Technology | Selective recovery |
| NZ718926A (en) | 2013-10-11 | 2021-12-24 | Massachusetts Eye & Ear Infirmary | Methods of predicting ancestral virus sequences and uses thereof |
| US10746742B2 (en) | 2014-04-25 | 2020-08-18 | Oregon Health & Science University | Methods of viral neutralizing antibody epitope mapping |
| US12146169B2 (en) * | 2018-05-30 | 2024-11-19 | Esteve Pharmaceuticals, S.A. | Adenoassociated virus vectors for the treatment of mucopolysaccharidoses type IV A |
| TW202039857A (zh) * | 2018-07-27 | 2020-11-01 | 美商銳進科斯生物股份有限公司 | 黏多醣病iva之治療 |
-
2021
- 2021-01-28 WO PCT/US2021/015436 patent/WO2021154956A1/en not_active Ceased
- 2021-01-28 EP EP21707517.5A patent/EP4097238A1/en not_active Withdrawn
- 2021-01-28 KR KR1020227027208A patent/KR20220133900A/ko not_active Withdrawn
- 2021-01-28 CA CA3168251A patent/CA3168251A1/en active Pending
- 2021-01-28 JP JP2022546078A patent/JP2023512043A/ja active Pending
- 2021-01-28 TW TW110103306A patent/TW202136516A/zh unknown
- 2021-01-28 US US17/792,969 patent/US20230064077A1/en not_active Abandoned
- 2021-01-28 AR ARP210100217A patent/AR121201A1/es unknown
- 2021-01-28 IL IL294638A patent/IL294638A/en unknown
- 2021-01-28 AU AU2021212749A patent/AU2021212749A1/en not_active Abandoned
- 2021-01-28 BR BR112022015036A patent/BR112022015036A2/pt not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| KR20220133900A (ko) | 2022-10-05 |
| WO2021154956A1 (en) | 2021-08-05 |
| EP4097238A1 (en) | 2022-12-07 |
| JP2023512043A (ja) | 2023-03-23 |
| AR121201A1 (es) | 2022-04-27 |
| CA3168251A1 (en) | 2021-08-05 |
| IL294638A (en) | 2022-09-01 |
| US20230064077A1 (en) | 2023-03-02 |
| BR112022015036A2 (pt) | 2022-10-11 |
| AU2021212749A1 (en) | 2022-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7619958B2 (ja) | 組換えアデノ随伴ウイルス及びその使用 | |
| JP7037574B2 (ja) | 脊髄性筋萎縮症の治療に有用な組成物 | |
| US20250001006A1 (en) | Recombinant adeno-associated viruses for targeted delivery | |
| US12247213B2 (en) | Treatment of mucopolysaccharidosis IVA | |
| WO2022076750A2 (en) | Recombinant adeno-associated viruses for cns or muscle delivery | |
| CA3162020A1 (en) | Compositions for treating friedreich's ataxia | |
| JP7534290B2 (ja) | Gm1ガングリオシドーシスの治療に有用な組成物 | |
| US20250051740A1 (en) | Treatment of mucopolysaccharidosis ii with recombinant human iduronate-2-sulfatase (ids) produced by human neural or glial cells | |
| CN118401667A (zh) | 用于治疗cdkl5缺乏症(cdd)的组合物 | |
| WO2023201277A1 (en) | Recombinant adeno-associated viruses for cns tropic delivery | |
| TW202045728A (zh) | 用於治療克拉培氏病之組成物 | |
| US20230064077A1 (en) | Treatment of mucopolysaccharidosis iva | |
| JP2023513487A (ja) | Gm1ガングリオシドーシスを治療するのに有用な組成物 | |
| US20230374541A1 (en) | Recombinant adeno-associated viruses for cns or muscle delivery | |
| US20260115322A1 (en) | Recombinant tert-encoding viral genomes and vectors | |
| WO2025132267A1 (en) | Plasmids, transgenes, vectors and medical uses comprising tissue non-specific alkaline phosphatase |